Susanna Fletcher Greer: To the ‘think tank’ – this researcher has an unlikely ally helping her impact pediatric cancer

Susanna Fletcher Greer, Chief Scientific Officer at the V Foundation, posted on LinkedIn:

“When a child is diagnosed with cancer, families are suddenly thrust into a world of uncertainty, with more questions than answers. One of the most devastating forms of childhood cancer is neuroblastoma, a tumor that arises from nerve tissue and often strikes infants and young children. Some neuroblastomas are surprisingly benign, disappearing on their own. Others can be relentless, spreading quickly, resisting treatment, and returning with a vengeance.

Researchers have long struggled to understand what causes these differences and, more importantly, how to predict and treat the most dangerous cases. Now, thanks to a groundbreaking study funded in part by the V Foundation, Dr. Madeline Hayes, PhD an Assistant Professor at The Hospital for Sick Children is beginning to unravel those mysteries, and Dr. Hayes and team are doing it with the help of an unlikely ally: the zebrafish. 

Zebrafish might seem like an odd choice for cancer research, but these tiny, transparent creatures are a powerful tool for understanding human disease. Because they share a surprising amount of genetic similarity with humans, Dr. Hayes and team engineer zebrafish to carry the same mutations found in children with cancer, allowing them to ‘watch’ tumors develop and spread in basically real time.

In this study, the Hayes lab focused on a group of genes involved in the DNA damage response, a cellular repair system that ‘fixes’ broken DNA. When these genes don’t work right, it’s like disabling the brakes on a car; cells can grow out of control, leading to cancer.

The Hayes team introduced mutations in several DNA damage response genes into a zebrafish neuroblastoma model. What Dr. Hayes found was striking: tumors in fish with these mutations were more aggressive, appeared earlier, and spread more widely. These findings confirm what previous studies had hinted at: that some kids with neuroblastoma carry hidden genetic vulnerabilities that drive the disease’s most dangerous forms.

But this story doesn’t end here. Just as important as understanding what makes these cancers tick is finding a way to stop them. Dr. Hayes and team tested how these mutant tumors responded to drugs already in use for other cancers. The results were promising! Zebrafish tumors with DNA damage response mutations were sensitive to a class of drugs known as PARP inhibitors, and combining with another drug called an ATR inhibitor, amplified the treatment’s effectiveness. (!!!)

This is where these findings could become a game changer. These drug combinations already exist, and they’re being tested in adult cancers. Now, thanks to this study, there’s strong evidence they could work in children with neuroblastoma, too, especially those whose tumors have specific genetic mutations. It’s a shift toward precision medicine: using a child’s individual genetic profile to guide therapy, rather than applying a one-size-fits-all approach.

Beyond offering hope for new treatments, this study also has major implications for how we screen and monitor children. These findings suggest that these mutations could be more relevant to pediatric cancers than previously thought and, as genetic testing becomes more common in cancer diagnosis, may soon allow identification of high-risk patients earlier and matching them with targeted therapies that dramatically improve their outcomes.

Bottom line: in a field where time is often measured in months or even weeks, the ability to rapidly identify and test promising treatments could be life-saving. For families facing a diagnosis of high-risk neuroblastoma, this research represents more than just scientific progress, it offers real hope for new therapies that are smarter, more targeted, and more effective.

The V Foundation support of this research is helping move pediatric cancer treatment into the future. By revealing the hidden vulnerabilities in childhood tumors and finding new ways to attack them, this work is building a bridge from the lab bench to the bedside, one zebrafish at a time.”